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Animal Eggs No Good for Human Cloning

Only human eggs can reprogram human DNA.

February 2, 2009

A shortage of human
eggs has been the major impediment to human cloning, so scientists have
been trying to use animal eggs instead, a controversial approach that has raised
fears of human-animal hybrids. Now new research suggests that using animal
eggs as surrogates won’t be successful.

The image shows the development of a human-bovine cloned embryo (top) and a human-rabbit cloned embryo (bottom). Credit: CLONING AND STEM CELLS, 2009Mary Ann
Liebert Inc.

In therapeutic cloning (or somatic cell nuclear transfer),
scientists transplant DNA from an adult skin cell into an egg that has had its
DNA removed. Unknown factors in the egg reprogram the adult DNA to resemble
embryonic DNA, and, in theory, the cell begins to develop like a normal embryo.
Scientists would like to create stem cells from cloned human embryos, both for
research and potentially for therapy: the cells would be genetically matched to
their human donors and thus could be transplanted without fear of rejection. But no
one has yet accomplished this with human cells and eggs.

The creation of human-animal hybrids has been a subject of
great debate in the United Kingdom, where scientists won permission to use
rabbit and cow eggs in human cloning experiments in 2007. (This Q&A with Ian
Wilmut, the biologist who spearheaded the cloning of the now renowned sheep Dolly, explores the controversy.) Similar research involving rabbit eggs has taken place in the United States, but with little government regulation here, there has been much less public debate.

A paper published today in Cloning and Stem Cells could
make the debate moot. A comparison of gene expression in human cells
transplanted into both human eggs and animal eggs suggests that animal eggs simply don’t
have the power to reprogram human DNA. Here’s an extract from a press release issued by Advanced Cell Technology (ACT), which sponsored the research.

Although human-to-human
clones (human clones) and human-to-animal clones (hybrids) appear similar, the
pattern of reprogramming of the donor human cell is dramatically
different. This study … shows for the
first time that the donor DNA in the cloned human embryos is extensively
reprogrammed through extensive up-regulation (“turning on” of genes) with
similar expression patterns to normal human embryos. Nearly all of the key differentially-expressed
genes were activated in the human clones.
In distinct contrast, the majority of these genes were down-regulated or
silenced in the human-animal hybrids.

Wilmut, who edits the journal, said in a statement, “This
very important paper suggests that livestock oocytes are extremely unlikely to
be suitable as recipients for use in human nuclear transfer. This is very
disappointing because it would mean that production of patient-specific stem
cells by this means would be impracticable.”

In the last year, scientists
have been experimenting with a new method of reprogramming, which skips the egg altogether and
instead uses several genetic factors to directly modify DNA. The ACT
researchers also examined expression of these key genes and found that they
were activated in both normal and cloned human embryos but not in the
human-animal hybrids. “The human-animal hybrids showed no difference or a
down-regulation of these critical pluripotency genes–effectively silencing
them–thus making the generation of stem cells impossible. Without appropriate
reprogramming, these data call into question the potential use of animal-egg
sources to generate patient-specific stem cells,” said Robert Lanza, chief
scientific officer at ACT, in an e-mail.

Some say that the characterization of reprogramming in human
clones is the most interesting aspect of the research. According to an article in
the Scientist,

The gene expression profiles now “lay the
foundation” for other detailed molecular analyses of human-human clones
with an eye toward isolating embryonic stem cells, said [Keith
Latham, a developmental biologist at Temple University School of Medicine,
in Philadelphia, who was not involved in the research]. [Justin St. John of
Warwick University] agreed that the paper’s most important finding was the
detailed characterization of human-human embryos, not the limited human-animal
hybrid data. “That in and of itself is a success,” he said. “I’m
not sure why they weren’t selling that point more … They seem to [be] spinning a
negative result instead of spinning [a] positive result.”

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